2H7B

Solution structure of the eTAFH domain from the human leukemia-associated fusion protein AML1-ETO

2H7B の概要

• エントリーDOI: 10.2210/pdb2h7b/pdb
• NMR情報: BMRB: 7147
• 分子名称: Core-binding factor, ML1-ETO (1 entity in total)
• 機能のキーワード: 4 helix bundle, transcription
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 11887.72

構造登録者

Plevin, M.J.,Zhang, J.,Guo, C.,Roeder, R.G.,Ikura, M. (登録日: 2006-06-01, 公開日: 2006-07-11, 最終更新日: 2024-05-29)

主引用文献

Plevin, M.J.,Zhang, J.,Guo, C.,Roeder, R.G.,Ikura, M.
The acute myeloid leukemia fusion protein AML1-ETO targets E proteins via a paired amphipathic helix-like TBP-associated factor homology domain
Proc.Natl.Acad.Sci.USA, 103:10242-10247, 2006

PubMed Abstract: Up to 15% of acute myeloid leukemias (AMLs) are characterized by the abnormal expression of the eight-twenty-one (ETO) transcriptional corepressor within an AML1-ETO fusion protein. The t(8;21) chromosomal translocation serves not only to disrupt WT AML1 function but also to introduce ETO activity during hematopoiesis. AML1-ETO was recently shown to inhibit E protein transactivation by physically displacing WT coactivator proteins in an interaction mediated by ETO. Here, we present the 3D solution structure of the human ETO TAFH (eTAFH) domain implicated in AML1-ETO:E protein interactions and report an unexpected fold similarity to paired amphipathic helix domains from the transcriptional corepressor Sin3. We identify and characterize a conserved surface on eTAFH that is essential for ETO:E protein recognition and show that the mutation of key conserved residues at this site alleviates ETO-based silencing of E protein transactivation. Our results address uncharacterized aspects of the corepression mechanism of ETO and suggest that eTAFH may serve to recruit ETO (or AML1-ETO) to DNA-bound transcription factors. Together, these findings imply that a cofactor exchange mechanism, analogous to that described for E protein inhibition, may represent a common mode of action for ETO.

PubMed: 16803958
DOI: 10.1073/pnas.0603463103

実験手法

SOLUTION NMR